The overall goal of the City of Hope Lymphoma SPORE is to develop translational studies to improve the detection and therapy of Hodgkin's and non-Hodgkin's Lymphoma. This application consisting of four translational research projects and five cores will develop novel approaches that are derived from molecular and immunologic studies of T-cell and antibody-based therapies. An important theme of the translational studies in this grant is to develop lymphoma therapies that will reduce toxicities associated with current treatment regimens for Hodgkin's and non-Hodgkin's Lymphoma which can then be translated to the older patient population. One major goal is to develop anti-CD30 based radioimmunotherapy for both Hodgkin's and CD30+ non-Hodgkin's Lymphoma. A Second Project will study the effectiveness of cellular immunotherapy for follicular lymphoma utilizing engineered CD19-specific T-cells. Investigators in this project have developed a T-cell genetic modification platform for expressing chimeric immunoreceptors that redirect antigen specificity and effector function of T-cells towards cell surface epitopes on lymphomas. Because epidemiologic studies indicate that stem cell damage from pretransplant therapeutic exposures may play a role in the development of myelodysplasia, a Third Project will longitudinally study a population of patients with Hodgkin's and non-Hodgkin's Lymphoma to investigate the cellular and molecular factors that are predictive for development of myelodysplasia, and to determine the molecular sequence of events that lead to myelodysplasia. In a Fourth Project, investigators will develop molecularly engineered constructs for anti-CD20 directed therapeutics to improve imaging, radioimmunotherapy, and novel immunocytokines for the treatment of patients with CD20+ lymphoma. An important component of this project will be to delineate the immunologic effector mechanisms operative in immunocytokine-mediate anti-lymphoma in vivo activity. The projects in this Lymphoma SPORE will be supported by five cores including: Administration, Biostatistics and Data Management, Tissue Bank for molecular and cellular studies, Biological Material Production, and Animal Models and Assays. This Lymphoma SPORE will also support a Developmental Research Program and a Career Development Program to foster the advancement of pilot translational research projects and young investigators focused on lymphoma.